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Prof Corrado Santocanale

Professor of Molecular Medicine
SFI Principal Investigator

Research interests

  • Mechanisms of genome replication: function and regulation of Cdc7 kinase
  • Cancer therapeutics

Research overview

 

Chromatin replication involves duplicating DNA while maintaining the epigenetic information. These processes are critical for genome stability and for preserving cell-type identity.

Uncontrolled entry into S-phase is one of the hallmarks of cancer, while defects in the replication machinery and in the proper maintenance of the epigenetic information can lead to tumorigenesis.

Our laboratory is interested in studying the mechanisms that regulate genome replication in human cancer cells with particular emphasis on the Cdc7 kinase. Cdc7 acts as a molecular switch for DNA synthesis and is also thought to participate in several other processes that regulate normal cell cycle progression and chromosome dynamics.

The identification of new substrates and the characterization of the physiological processes in which Cdc7 is involved, will be pivotal in understanding in what disease context emerging Cdc7 inhibitors may be used for the cancer treatment, and in developing novel biomarkers, thus providing valuable information and tools for rationally driving patient selection and devising combination therapies in preclinical and clinical settings.

We have recently established a novel technique for the purification and characterization of proteins associated to newly replicated DNA that we call DNA mediated chromatin pull down (Dm-ChP).

This technique holds the promise for rapid advance in understanding how DNA synthesis and chromatin assembly are coordinated.

For further information on the Santocanale lab or to meet the lab members click here

Selected publications

  • Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C, DNA mediated chromatin pull-down for the study of chromatin replication. Sci Rep 1: 95 (2011)
  • Natoni A, Murillo LS, Kliszczak AE, Catherwood MA, Montagnoli A, Samali A, O'Dwyer M, Santocanale C, Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells. Mol Cancer Ther 10: 1624-1634 (2011)
  • Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C, A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol 4: 357-365 (2008)